Since FMR response to CRT is of prognostic importance, and this response is impaired by AF, mitigating the negative influence of AF on FMR is an attractive therapeutic strategy. In 330 patients with permanent AF who received CRT, 34 (10.3%) spontaneously recovered SR at 4 months.26 In contrast, in a study of 74 patients (27% with persistent AF and 73% with permanent AF), CRT did not induce spontaneous conversion to SR in any patient at 6 months of follow-up.27 With the current findings, it is unclear if awaiting a spontaneous return to SR after CRT is the optimal strategy. Various additional treatment options could be considered
7
107
Atrial fibrillation and improvement of mitral regurgitation in CRT
to restore SR in AF patients, including pharmacological and electrical cardioversion, as well as catheter ablation. In a study by Gertz et al. 53 patients with moderate to severe FMR who underwent AF catheter ablation, the mitral annular dimension was significantly larger in those with recurrent AF compared to patients who remained in SR (3.48±0.34 cm vs. 3.24±0.32 cm, respectively; P=0.06) at one year.28 In the same study, the LA volume was larger in patients with recurrent AF as compared to patients who remained in SR (66.4±18.4 ml vs. 52.4±12.7 ml, respectively; P=0.02) at one year follow-up.28 Moreover, significant FMR at one year follow-up was observed in 24% of patients in SR as compared to 82% in patients with AF at one year follow-up (P=0.005).28 Although this study was not performed in patients undergoing CRT, the results suggest that AF ablation has the potential to reduce FMR in CRT recipients by reducing LA volume and mitral annular diameter.
Currently, one trial investigated AF recurrence after radiofrequency catheter ablation in patients who previously underwent CRT; Di Biase et al. randomized CRT recipients to AF ablation or amiodarone use, with a minimum follow-up of 2 years.6 The recurrence of AF was significantly lower in the patients undergoing ablation as compared to the patients using amio- darone (30% vs. 66%, respectively; P<0.001) and a significant mortality difference was observed in favour of ablation (8% vs. 18%; P=0.037).6 The concept of an atrial myopathy has gained
Figure 5: Differences in mitral annular remodeling, when measured in apical 4-chamber view and parasternal, long-axis view. The decrease in mitral annular diameter is much more pronounced when measured in the parasternal long-axis view, compared to the apical 4-chamber view. This likely reflects the fact that long-axis measurement (red line) transects the fixed annulus (solid grey line) and the unsupported part (dashed, grey line), while the apical 4- chamber measurement (green line) may still transect a second, fixed part of the mitral fibrous skeleton (solid grey line) in some patients. This will therefore underestimate the effect of cardiac resynchronization therapy on mitral annular remodeling. Ao: aorta, MV: mitral valve, TV: tricuspid valve.
Clinical implications
Since FMR response to CRT is of prognostic importance, and this response is impaired by AF, mitigating the negative influence of AF on FMR is an attractive therapeutic strategy. In 330 patients with permanent AF who received CRT, 34 (10.3%) spontaneously recovered SR at 4 months.26In contrast, in a study of 74 patients (27% with persistent AF and 73% with
permanent AF), CRT did not induce spontaneous conversion to SR in any patient at 6 months of follow-up.27 With the current findings, it is unclear if awaiting a spontaneous return to SR
after CRT is the optimal strategy. Various additional treatment options could be considered to restore SR in AF patients, including pharmacological and electrical cardioversion, as well as catheter ablation. In a study by Gertz et al. 53 patients with moderate to severe FMR who underwent AF catheter ablation, the mitral annular dimension was significantly larger in those with recurrent AF compared to patients who remained in SR (3.48±0.34 cm vs. 3.24±0.32 cm,
Figure 5: Differences in mitral annular remodeling, when measured in apical 4-chamber view and paraster- nal, long-axis view. The decrease in mitral annular diameter is much more pronounced when measured in the parasternal long-axis view, compared to the apical 4-chamber view. This likely reflects the fact that long- axis measurement (red line) transects the fixed annulus (solid grey line) and the unsupported part (dashed, grey line), while the apical 4- chamber measurement (green line) may still transect a second, fixed part of the mitral fibrous skeleton (solid grey line) in some patients. This will therefore underestimate the effect of car- diac resynchronization therapy on mitral annular remodeling. Ao: aorta, MV: mitral valve, TV: tricuspid valve.
Chapter 7
108
attention in recent years, with those having more advanced electromechanical atrial disease (e.g. fibrosis, visualized with cardiac magnetic resonance imaging) responding less well to catheter ablation.29 It is not inconceivable that patients with advanced atrial myopathy and/or long-standing AF will also respond suboptimally to ablative therapy in terms of FMR reduction. Even though the success rate of AF ablation is more variable in persistent and long-standing AF, mitral annular reverse remodeling and a decrease in AF recurrence in CRT patients were seen in those studies where such patients were included.6, 28
Recently, the Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial demonstrated lower all-cause mortality and heart failure hospitalization in heart failure patients with AF who underwent catheter ablation, when compared to medical therapy.30 Of the patients who underwent ab- lation, 27% had a CRT device in situ.30 Although reduction in FMR was not reported, this trial provides further support for the role of catheter ablation in the management of AF in heart failure patients, including those with CRT.
Study limitations
This was a single-center, retrospective study. The severity of FMR can be influenced by different hemodynamic conditions, although only hemodynamically stable patients were included in the current analysis. The differences between the amount of change in chamber dimensions (Table 2) of CRT recipients with SR and AF at baseline, have to be interpreted cautiously due to fairly large standard deviations.
CONCLUSIONS
Improvement of FMR is more often observed in CRT recipients in SR at baseline, as compared to patients with AF at baseline, despite a similar degree of LV reverse remodeling at 6 months after CRT. LA volume and mitral annular diameter are larger at 6 months in the patients with AF at baseline, suggesting that these mechanisms may relate to the adverse effect of AF on FMR improvement following CRT. AF rhythm control (especially by means of catheter ablation) is therefore a potential therapeutic target to improve FMR after CRT in patients with AF, although the response in those with permanent AF may be variable, compared to paroxysmal AF.
7
109
Atrial fibrillation and improvement of mitral regurgitation in CRT
REFERENCES
1. Bursi F, Enriquez-Sarano M, Nkomo VT et al. Heart failure and death after myocardial infarction in the community: the emerging role of mitral regurgitation. Circulation 2005;111:295-301.
2. Rossi A, Dini FL, Faggiano P et al. Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non- ischaemic dilated cardiomyopathy. Heart 2011;97:1675-80.
3. Spartera M, Galderisi M, Mele D et al. Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation. Eur Heart J Cardiovasc Imaging 2016;17:471-80.
4. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-200.
5. Tanimoto M, Pai RG. Effect of isolated left atrial enlargement on mitral annular size and valve competence. Am J Cardiol 1996;77:769-74.
6. Di Biase L, Mohanty P, Mohanty S et al. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: results from the AATAC multicenter randomized trial. Circulation 2016;133:1637-44.
7. Swedberg K, Olsson LG, Charlesworth A et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J 2005;26:1303-8.
8. Hoppe UC, Casares JM, Eiskjær H et al. Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure. Circulation 2006;114:18-25.
9. Brignole M, Auricchio A, Baron-Esquivias G et al. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281-329.
10. Lellouche N, De Diego C, Vaseghi M et al. Cardiac resynchronization therapy response is associated with shorter duration of atrial fibrillation. Pacing Clin Electrophysiol 2007;30:1363-8.
11. Van der Bijl P, Khidir M, Leung M et al. Impact of QRS complex duration and morphology on left ventricular reverse remodelling and left ventricular function improvement after cardiac resynchro- nization therapy. Eur J Heart Fail 2017;19:1145-51.
12. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962.
13. Lang RM, Badano LP, Mor-Avi V et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233-70. 14. Lancellotti P, Tribouilloy C, Hagendorff A et al. Recommendations for the echocardiographic as-
sessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2013;14:611-44.
15. Bertini M, Hoke U, van Bommel RJ et al. Impact of clinical and echocardiographic response to cardiac resynchronization therapy on long-term survival. Eur Heart J Cardiovasc Imaging 2013;14:774-81.
Chapter 7
110
16. Gold MR, Daubert C, Abraham WT et al. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: results of the REVERSE study. Heart Rhythm 2015;12:524-30.
17. Breithardt OA, Sinha AM, Schwammenthal E et al. Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol 2003;41:765- 70.
18. Porciani MC, Macioce R, Demarchi G et al. Effects of cardiac resynchronization therapy on the me- chanisms underlying functional mitral regurgitation in congestive heart failure. Eur J Echocardiogr
2006;7:31-9.
19. Gasparini M, Auricchio A, Regoli F et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 2006;48:734-43.
20. Otsuji Y, Kumanohoso T, Yoshifuku S et al. Isolated annular dilation does not usually cause important functional mitral regurgitation: comparison between patients with lone atrial fibrillation and those with idiopathic or ischemic cardiomyopathy. J Am Coll Cardiol 2002;39:1651-6.
21. Silbiger JJ. Does left atrial enlargement contribute to mitral leaflet tethering in patients with functional mitral regurgitation? Proposed role of atriogenic leaflet tethering. J Heart Valve Dis
2014;23:385-6.
22. Wozakowska-Kaplon B. Changes in left atrial size in patients with persistent atrial fibrillation: a prospective echocardiographic study with a 5-year follow-up period. Int J Cardiol 2005;101:47-52. 23. Kihara T, Gillinov AM, Takasaki K et al. Mitral regurgitation associated with mitral annular dilation in
patients with lone atrial fibrillation: an echocardiographic study. Echocardiography 2009;26:885-9. 24. Yu CM, Fang F, Zhang Q et al. Improvement of atrial function and atrial reverse remodeling after
cardiac resynchronization therapy for heart failure. J Am Coll Cardiol 2007;50:778-85.
25. Kanzaki H, Bazaz R, Schwartzman D et al. A mechanism for immediate reduction in mitral regurgita- tion after cardiac resynchronization therapy: insights from mechanical activation strain mapping. J Am Coll Cardiol 2004;44:1619-25.
26. Gasparini M, Steinberg JS, Arshad A et al. Resumption of sinus rhythm in patients with heart failure and permanent atrial fibrillation undergoing cardiac resynchronization therapy: a longitudinal ob- servational study. Eur Heart J 2010;31:976-83.
27. Kies P, Leclercq C, Bleeker GB et al. Cardiac resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and reversal to sinus rhythm. Heart 2006;92:490-4.
28. Gertz ZM, Raina A, Saghy L et al. Evidence of atrial functional mitral regurgitation due to atrial fibrillation: reversal with arrhythmia control. J Am Coll Cardiol 2011;58:1474-81.
29. Goldberger JJ, Arora R, Green D et al. Evaluating the atrial myopathy underlying atrial fibrillation: identifying the arrhythmogenic and thrombogenic substrate. Circulation 2015;132:278-91. 30. Marrouche NF, Brachmann J, Andresen D et al. Catheter ablation for atrial fibrillation with heart